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Morpholino-mediated knockdown of MTMR14 results in morphologic abnormalities, a developmental motor phenotype characterized by diminished spontaneous contractions and abnormal escape response, and impaired excitation-contraction coupling.
This study provides the first in vivo evidence for a role of myotubularins, and in particular MTMR14, in the regulation of autophagy.
The authors uncovered a key negative regulatory role in autophagy of a phosphatidylinositol 3-phosphate (PI3P) phosphatase Jumpy (MTMR14).
C3orf29 encodes hJUMPY, a phosphoinositide 3-phosphate phosphatase that acts on PtdIns3P and PtdIns(3,5)P2. A missense mutation disrupts the catalytic activity in a patient with centronuclear myopathy.
Data (including data from studies in knockout mice) suggest that Mtmr14 plays role in lipid metabolism and inflammation in liver, skeletal muscle, and adipose tissue in obesity induced by high-fat diet (HFD); here, Mtmr14 deficiency in knockout mice accelerates HFD-induced inflammation and metabolic dysfunction (obesity, hyperglycemia, and hyperlipidemia).
propose that defect of MTMR14 promotes autophagy and cell proliferation in MEFs
In young Mtmr14 KO mice (12 weeks). The T-tubule dysmorphology (swollen and elongated) could explain, in part, the defects in Ca2thorn excitationcontraction machinery observed in previous studies.
MTMR14 may play an important role in muscle calcium homeostasis.
Data report that mice deficient in the newly identified phosphatidylinositol phosphate phosphatase MIP (show MIP Antibodies)/MTMR14 (muscle-specific (show EIF3K Antibodies) inositol phosphatase) show muscle weakness and fatigue.
This gene encodes a myotubularin-related protein. The encoded protein is a phosphoinositide phosphatase that specifically dephosphorylates phosphatidylinositol 3,5-biphosphate and phosphatidylinositol 3-phosphate. Mutations in this gene are correlated with autosomal dominant centronuclear myopathy. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 18.
myotubularin related protein 14
, myotubularin-related protein 14-like
, HCV NS5A-transactivated protein 4 splice variant A-binding protein 1
, egg-derived tyrosine phosphatase homolog
, myotubularin-related protein 14